Study on brain protective effect of 20% lipid emulsion combined with pralidoxime and atropine on organophosphate poisoning mice

doi:10.16138/j.1673-6087.2025.04.07

Abstract

Abstract:

Objective To investigate the therapeutic effect of pralidoxime combined with atropine and lipid emulsion on a mouse model of organophosphate poisoning. Methods Eighty C57/BL6 strain experimental mice were randomly divided into four groups of 10 each using a digital randomization method. A mouse organophosphate poisoning model was established using organophosphate pesticides. Pralidoxime combined with atropine and lipid emulsion was used for treatment. Results The results showed that compared with the poisoning group, the mice in the treatment group showed significant improvement in physiological indexes such as fasciculation tremor intensity and anti-reflex disappearance time (all P<0.001). In particular, the effect was more pronounced in the combination treatment group with pralidoxime, atropine, and lipid emulsion. In addition, the combination therapy effectively improve the serum levels of acetylcholinesterase (AchE), malondialdehyde (MDA) and S100 calcium binding protein B (S100B) in the poisoning mice (all P<0.001) and promoted the recovery of these biochemical indicators to normal levels after 7 days. In the behavioral test, the number of correct responses in the Y-maze test was significantly higher in the treatment group than in the poisoning group, especially in the mice receiving the combination treatment (all P<0.001). Histopathological examinations showed that the combination of clofosidine and atropine could significantly reduce the brain tissue damage caused by poisoning, and the effect was more significant after the addition of lipid emulsion. Conclusions Pralidoxime combined with atropine can effectively alleviate the symptoms of organophosphate poisoning in mice, and the addition of lipid emulsion can further optimize the therapeutic effect, providing a new treatment strategy for clinical practice.

Key words: Organophosphate poisoning, Atropine, Pralidoxime, Fat emulsion

CLC Number:

R595.4

GAO Hui, YANG Chao, HU Xiaofeng. Study on brain protective effect of 20% lipid emulsion combined with pralidoxime and atropine on organophosphate poisoning mice[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(04): 301-305.

Figures/Tables 4

Table 1

Table 2

Table 3

Figure 1

References 21

[1]	Yu SY, Gao YX, Walline J, et al. Role of penehyclidine in acute organophosphorus pesticide poisoning[J]. World J Emerg Med, 2020, 11(1):37-47.
[2]	Hulse EJ, Haslam JD, Emmett SR, et al. Organophosphorus nerve agent poisoning: managing the poisoned patient[J]. Br J Anaesth, 2019, 123(4):457-463. doi: S0007-0912(19)30401-5 pmid: 31248646
[3]	Eddleston M. Novel clinical toxicology and pharmacology of organophosphorus insecticide self-poisoning[J]. Annu Rev Pharmacol Toxicol, 2019, 59:341-360. doi: 10.1146/annurev-pharmtox-010818-021842 pmid: 30230960
[4]	Twayana S, Sharma VK, Raut M, et al. Mean serum creatine kinase among organophosphate poisoning cases in a tertiary care centre: a descriptive cross-sectional study[J]. JNMA J Nepal Med Assoc, 2022, 60(254):881-893. doi: 10.31729/jnma.7692 pmid: 36705158
[5]	Patil A, Kumar S, Inamdar A, et al. Impact of serum amylase level in the outcome of acute organophosphorus poisoning: 2-year cross-sectional study at rural teaching hospital[J]. J Lab Physicians, 2022, 14(1):1-5. doi: 10.1055/s-0041-1734015 pmid: 36186263
[6]	Rambabu L, Megson IL, Eddleston M. Does oxidative stress contribute to toxicity in acute organophosphorus poisoning?[J]. Clin Toxicol (Phila), 2020, 58(6):437-452.
[7]	Antonijevic E, Kotur-Stevuljevic J, Musilek K, et al. Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain[J]. Arch Toxicol, 2018, 92(2):745-757. doi: 10.1007/s00204-017-2101-z pmid: 29098328
[8]	胡小东, 周春, 康向飞, 等. 脂肪乳对有机磷农药中毒大鼠肝损伤的保护作用研究[J]. 宁夏医学杂志, 2021, 43(10):872-874.
	Hu XD, Zhou C, Kang XF, et al. Protective effect of lipid emulsion on liver injury in rats with acute organophosphorus poisoning[J]. Ningxia Med J, 2021, 43(10):872-874.
[9]	李刚, 韩楠楠, 张可, 等. 脂肪乳通过 LPS/TLR4 通路对急性有机磷中毒肺损伤的治疗作用研究[J]. 重庆医学, 2022, 51(9):1448-1451.
	Li G, Han NN, Zhang K, et al. Therapeutical effect of lipid emulsion in lung damage induced by acute organophosphorus poisoning through LPS/TLR4 pathway[J]. Chongqing Med, 2022, 51(9):1448-1452.
[10]	Kharel H, Pokhrel NB, Ghimire R, et al. The Efficacy of pralidoxime in the treatment of organophosphate poisoning in humans: a systematic review and meta-analysis of randomized trials[J]. Cureus, 2020, 12(3):e7174.
[11]	王建星, 郭笑妍. 长托宁与氯解磷定联合血液灌流对急性重度有机磷农药中毒患者CRP和PCT及心肌酶的影响[J]. 武警后勤学院学报, 2021, 30(6):76-78.
	Wang JX, Guo XY. Effects of penehyclidine hydrochloride and pralidoxime chloride combined with hemoperfusion on CRP,PCT and myocardial enzymes in patients with acute severe organophosphorus pesticide poisoning[J]. J Log Univ PAP( Med Sci), 2021, 30(6):76-78.
[12]	Richardson KJ, Schwincks JL, Robinson MV. Organophosphate poisoning[J]. Nurse Pract, 2021, 46(7):18-21. doi: 10.1097/01.NPR.0000743328.87750.d7 pmid: 34138808
[13]	Masson P, Nachon F. Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning[J]. J Neurochem, 2017, 142 Suppl 2:26-40. doi: 10.1111/jnc.14026 pmid: 28542985
[14]	Aman S, Paul S, Chowdhury FR. Management of organophosphorus poisoning: Standard treatment and beyond[J]. Crit Care Clin, 2021, 37(3):673-686. doi: 10.1016/j.ccc.2021.03.011 pmid: 34053713
[15]	Dhanarisci J, Tzotzolaki TM, Vasileva AD, et al. Osmolal and anion gaps after acute self-poisoning with agricultural formulations of the organophosphorus insecticides profenofos and diazinon[J]. Basic Clin Pharmacol Toxicol, 2022, 130(2):320-327.
[16]	王亚红. 急性重度有机磷农药中毒致呼吸衰竭患者的临床急诊急救措施[J]. 中国医学文摘(耳鼻咽喉科学), 2021, 36(2):85-86.
	Wang YH. Emergency clinical emergency measures for patients with respiratory failure caused by acute severe organophosphorus pesticide poisoning[J]. Chin Med Digest Otorhinolaryngol, 2021, 36(2):85-86.
[17]	傅萱, 张文武. 脂肪乳剂应用于急性中毒的研究进展[J]. 中华急诊医学杂志, 2016, 25(7):964-969.
	Fu X, Zhang WW. Advances in application of lipid emulsion in acute poisioning[J]. Chin J Emerg Med, 2016, 25(7):964-969.
[18]	Pannu AK, Garg S, Bhalla A, et al. Lipid emulsion for the treatment of acute organophosphate poisoning: an Open-Label randomized trial[J]. Clin Toxicol (Phila), 2022, 60(5):602-618.
[19]	Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges[J]. Anal Biochem, 2017, 524:13-30. doi: S0003-2697(16)30357-8 pmid: 27789233
[20]	Li J, Liu RH, Shan RB. Value of serum S100B protein and neuron-specific enolase levels in predicting the severity of hand, foot and mouth disease[J]. Zhongguo Dang Dai Er Ke Za Zhi, 2017, 19(2):182-187.
[21]	翟声平, 柴文戍, 任美华. Fas/FasL与氧自由基在肺纤维化大鼠细胞凋亡中的作用研究[J]. 中国全科医学, 2007, 10(9):711-713.
	Zhai SP, Chai WS, Ren MH. Change of Fas/FasL and oxyradical system on the pulmonart fibrosis rats[J]. Chin Gen Pract, 21. 2007, 10(9):711-713.

指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
肌束震颤强度（分）	0	3（3,3）^1）	2（2,2）^1）2）	2（1,2）^1）2）3）	34.536	<0.001
翻正反射消失时间（s）	0	345.700±36.576^1）	541.100±84.608^1）2）	650.300±122.405^1）2）3）	138.900	<0.001

指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
AChE(U/mL)	102.347±16.055	50.880±5.127^1）	73.491±6.843^1）2）	88.732±12.666^1）2）3）	118.9	<0.001
MDA(nmol/mL)	4.423±0.606	6.304±0.645^1）	5.339±0.545^1）2）	4.785±0.404^1）2）3）	64.770	<0.001
S100B(pg/mL)	62.700±14.305	155.731±11.5^1）2）	126.900±17.413^1）2）	111.221±11.511^1）2）3）	235.300	<0.001

指标	正常组	染毒组	氯解磷定联合阿托品组	氯解磷定+阿托品+脂肪乳剂组	F	P
AChE(U/mL)	100.843±16.080	47.871±8.759^1）	74.719±12.494^1）2）	82.988±13.343^1）2）3）	87.090	<0.001
MDA(nmol/mL)	4.472±0.469	7.036±1.048^1）	6.118±0.353^1）2）	5.364±0.736^1）2）3）	71.020	<0.001
S100B(pg/mL)	64.994±15.851	601.044±25.228^1）	476.553±25.960^1）2）	421.712±30.092^1）2）3）	2572.000	<0.001